OBJECTIVES: To systematically evaluate evidence for the detrimental impact of long-term therapy with preservative containing topical antiglaucoma treatments (P) in patients/subjects with glaucoma or ocular hypertension (OH) METHODS: Systematic review and qualitative synthesis of observational studies comparing the use of P and preservative-free (PF) treatments in patients/subjects with glaucoma or OH. RESULTS: Eleven studies met review inclusion criteria. Studies differed considerably in terms of design (cross sectional, case control, before-after), treatments recieved (nature and number of anti-glaucoma agents received, different nature and/or concentration of preservative) and duration of follow-up. Reported outcomes variously included subjective ocular symptoms, clinical measures of lacrymal function, sub-clinical markers of ocular surface change or inflammation and vision related quality of life (QoL). There were no reports of generic measures of QoL or long-term sequelae, e.g. requirement/ success of glaucoma-related surgery. The disparity of the studies meant that data were not amenable to statistical pooling. However, qualitatively, the studies provide a body of evidence which may support an association between the long-term use of P and an increase in subjective symptoms and clinical and sub clinical signs that are suggestive of damage to the ocular surface. The most common apparent side effect reported is dry-eye which directly affects vision related QoL. The expression of symptoms and signs of toxicity appear to be dose dependant and reversible when exposure to preservative is reduced or discontinued. However, the studies cannot exclude other contributory factors that may be inherent in topical therapy per se, e.g., the toxicity of the active agent itself and/or cumulative physical effects of administration. CONCLUSIONS: The findings suggest that the preservatives included in some topical antiglaucoma treatments may at least contribute to observed changes to the ocular surface, impairment of lachrymal function and more subjective symptoms experienced by patients.